ABSTRACT
Although osteosarcoma is a rare disease, with a global incidence rate estimated at 5.0/million/year, it is the most frequent primary bone sarcoma in children and adolescents. In translational research, the patient-derived xenograft (PDX) model is considered an authentic in vivo model for several types of cancer, as tumorgrafts faithfully retain the biological characteristics of the primary tumors. Our goal was to investigate the association between PDX formation and clinical findings of osteosarcoma patients and the ability of the model to preserve in immunocompromized mice the characteristics of the parental tumor. A fresh sample of the patient tumor obtained from a representative biopsy or from surgical resection was implanted into nude mice. When tumor outgrowths reached ~1,500mm³, fresh PDX fragments were re-transplanted into new hosts. Engraftment in mice was obtained after a latency period of 19-225 days (median 92 days) in 40.54% of the implanted samples. We confirmed the histopathological fidelity between the patient tumor and their respective established PDXs, including the expression of biomarkers. PDX take rate was higher in surgical resection samples, in post-chemotherapy surgical samples and in samples from patients with metastatic disease at presentation. In conclusion, we have shown that the osteosarcoma PDX model reliably recapitulates the morphological aspects of the human disease after serial passage in mice. The observation that more aggressive forms of osteosarcoma, including those with metastatic disease at presentation, have a higher efficiency to generate PDXs provides a promising scenario to address several unanswered issues in clinical oncology.
Subject(s)
Bone Neoplasms/pathology , Cell Proliferation , Osteosarcoma/secondary , Adolescent , Adult , Animals , Biomarkers, Tumor/metabolism , Bone Neoplasms/metabolism , Bone Neoplasms/surgery , Child , Female , Humans , Male , Mice, Nude , Middle Aged , Neoplasm Transplantation , Osteosarcoma/metabolism , Osteosarcoma/surgery , Phenotype , Time Factors , Transplantation, Heterologous , Tumor Burden , Young AdultABSTRACT
Our main objective was to evaluate the ophthalmic artery Doppler behavior in twin pregnancies and compare with singleton pregnancies. We studied 64 healthy twin pregnant women between 12 to 38 weeks of gestation. Resistance index (RI), pulsatility index (PI), and peak ratio (PR) were determined. The control group consisted of 289 singletons. Linear regression analysis was performed to evaluate the association between gestational age and the ophthalmic indexes. Student t test was used to compare the means and standard deviation of the Doppler indexes. There was a decrease in RI and PI and an increase in PR with advancing gestational age (ρ < 0.0001, 0.0052, and 0.0033). The means ± SDs for RI, PI, and PR were 0.77 ± 0.07, 1.79 ± 0.46, and 0.53 ± 0.12, in women with twin pregnancies and 0.75 ± 0.05, 1.88 ± 0.43, and 0.52 ± 0.10 in singletons. No significant difference was found between the PI and PR values, but significant difference was found in the RI values between the groups (P = 0.0332). We concluded that there are no significant differences in ophthalmic artery behavior in twins and the same reference values established in singleton pregnancies can be applied for PI and PR indexes in the evaluation of twin pregnancies. These indexes were the best to evaluate twin pregnancies.
Subject(s)
Ophthalmic Artery/physiology , Ultrasonography, Doppler/methods , Ultrasonography, Prenatal/methods , Adult , Blood Flow Velocity/physiology , Cross-Sectional Studies , Female , Humans , Pregnancy , Pregnancy, TwinABSTRACT
Objective To compare the endocrine cord blood characteristics of offspring from obese mothers with those of offspring from healthy controls. Methods Cross-sectional case control study. SETTING: University medical centers. PATIENT(S): Offspring from obese mothers (n = 41) and healthy controls (n = 31). INTERVENTION(S): Cord blood withdrawal from neonates. MAIN OUTCOME MEASURE(S): Cord blood total cholesterol (TC), triglycerides (TGs), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), blood glucose (GL) and insulin (Ins). Result(s) Fetal GL and TGs were reduced in the offspring of obese women when compared to those in the offspring of the controls. The mean cord blood GL level was 47.8 mg/dL standard deviation (SD 33.1) in the offspring of the obese group vs. 57.9 mg/dL (SD 12.5) in the offspring of the control group, and the mean cord blood TG level was 26.5 (SD 33.6) in the offspring of the obese group vs. 34.6 (SD 12.3) in the offspring of the control group. Maternal obesity was also associated with reduced levels of TC and HDL-C in the pregnant women. Conclusion The observed results suggest that GL and TGs in the cord blood of the offspring of obese mothers were significantly lower than those in the offspring of the control group.
Subject(s)
Fetal Blood/chemistry , Obesity/blood , Pregnancy Complications/blood , Adolescent , Adult , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Middle Aged , Pregnancy , Young AdultABSTRACT
BACKGROUND: In the present study, we used Doppler velocimetry in the ophthalmic artery to evaluate the hemodynamic status of the intracranial vasculature. This is the first time in the literature that indices of ophthalmic artery Doppler sonography of women with preeclampsia were evaluated before and after the use of magnesium sulfate to prevent eclampsia. CASE PRESENTATION: Indices of ophthalmic artery Doppler sonography of six women with severe preeclampsia at 27 to 33 weeks of gestational age were evaluated before and after the use of magnesium sulfate (10 minutes, 30 minutes, and 60 minutes after the magnesium sulfate loading dosage. The patients' ages were 26 years (patient 01), 29 years (patient 02), 20 years (patient 03), 21 years (patient 04), 20 years (patient 05), and 19 years (patient 06). The ethnic group of patients 01 and 04 was white and the ethnic group of patients 02, 03, 05 and 06 was mulatto. CONCLUSIONS: The apparent increase in resistance index and pulsatility index values, although there is no statistical significance in this series of cases, and the decrease in peak ratio values after the administration of magnesium sulfate reflect an increase in the impedance to flow in the ophthalmic artery and consequently a reduction in cerebral perfusion after the use of magnesium sulfate. This may explain how magnesium sulfate protects women with severe preeclampsia against cerebral damage and prevents acute convulsions in these patients. We believe that this case series report may have a broader clinical impact across medicine because the mechanism of how magnesium sulfate can protect patients and prevent acute convulsions is controversial.
Subject(s)
Magnesium Sulfate/pharmacology , Ophthalmic Artery/diagnostic imaging , Pre-Eclampsia/physiopathology , Tocolytic Agents/pharmacology , Ultrasonography, Doppler/methods , Administration, Intravenous , Adult , Analysis of Variance , Female , Gestational Age , Humans , Magnesium Sulfate/administration & dosage , Ophthalmic Artery/physiopathology , Pre-Eclampsia/drug therapy , Pregnancy , Rheology/instrumentation , Severity of Illness Index , Tocolytic Agents/administration & dosage , Young AdultABSTRACT
From the discovery of the Zika virus (ZIKV) in 1947 in Uganda (Africa), until its arrival in South America, it was not known that it would affect human reproductive life so severely. Today, damage to the central nervous system is known to be multiple, and microcephaly is considered the tip of the iceberg. Microcephaly actually represents the epilogue of this infection's devastating process on the central nervous system of embryos and fetuses. As a result of central nervous system aggression by the ZIKV, this infection brings the possibility of arthrogryposis, dysphagia, deafness and visual impairment. All of these changes of varying severity directly or indirectly compromise the future life of these children, and are already considered a congenital syndrome linked to the ZIKV. Diagnosis is one of the main difficulties in the approach of this infection. Considering the clinical part, it has manifestations common to infections by the dengue virus and the chikungunya fever, varying only in subjective intensities. The most frequent clinical variables are rash, febrile state, non-purulent conjunctivitis and arthralgia, among others. In terms of laboratory resources, there are also limitations to the subsidiary diagnosis. Molecular biology tests are based on polymerase chain reaction (PCR) with reverse transcriptase (RT) action, since the ZIKV is a ribonucleic acid (RNA) virus. The RT-PCR shows serum or plasma positivity for a short period of time, no more than five days after the onset of the signs and symptoms. The ZIKV urine test is positive for a longer period, up to 14 days. There are still no reliable techniques for the serological diagnosis of this infection. If there are no complications (meningoencephalitis or Guillain-Barré syndrome), further examination is unnecessary to assess systemic impairment. However, evidence is needed to rule out other infections that also cause rashes, such as dengue, chikungunya, syphilis, toxoplasmosis, cytomegalovirus, rubella, and herpes. There is no specific antiviral therapy against ZIKV, and the therapeutic approach to infected pregnant women is limited to the use of antipyretics and analgesics. Anti-inflammatory drugs should be avoided until the diagnosis of dengue is discarded. There is no need to modify the schedule of prenatal visits for pregnant women infected by ZIKV, but it is necessary to guarantee three ultrasound examinations during pregnancy for low-risk pregnancies, and monthly for pregnant women with confirmed ZIKV infection. Vaginal delivery and natural breastfeeding are advised.
Desde a descoberta do vírus Zika (VZIK) em 1947 em Uganda, na África, até sua chegada na América do Sul, não se tinha notícia de que ele seria capaz de comprometer a vida reprodutiva em humanos de forma tão severa. Hoje, sabe-se que os danos sobre o sistema nervoso central são múltiplos, e a microcefalia é considerada a ponta do iceberg, visto que na realidade ela representa o epílogo de um processo devastador desta infecção sobre o sistema nervoso central do embrião e do feto. Em decorrência da agressão do sistema nervoso central pelo VZIK, esta infecção pode provocar artrogripose, disfagia, surdez e comprometimento visual. Todas estas alterações, de gravidade variável, direta ou indiretamente comprometem a vida futura dessas crianças, já sendo considerada uma síndrome congênita ligada ao VZIK. Uma das principais dificuldades na abordagem dessa infecção é relativa ao diagnóstico. Considerando a parte clínica, observa-se que ela apresenta manifestações comuns às infecções pelos vírus da dengue e da febre chikungunya, variando apenas em suas intensidades subjetivas. As variáveis clínicas mais frequentes são o exantema, febrícula, conjuntivite não purulenta e artralgia. No tocante aos recursos laboratoriais, também existem limitações ao diagnóstico subsidiário. As provas de biologia molecular se fundamentam na reação em cadeia da polimerase (RCP) com ação da transcriptase reversa (TT), visto que o VZIK é um vírus ácido ribonucleico (ARN). A TR-RCP apresenta positividade sérica ou plasmática por um período curto de tempo, não ultrapassando cinco dias após início dos sinais e sintomas. Esta pesquisa do VZIK na urina fica positiva por período mais prolongado, chegando a 14 dias. Ainda não existem técnicas seguras para diagnóstico sorológico dessa infecção. Não havendo complicações (meningoencefalite ou síndrome de Guillain-Barré), dificilmente são necessários mais exames complementares para avaliar o comprometimento sistêmico. No entanto, são necessárias provas para descartar as outras infecções que causam exantema, como dengue, chikungunya, sífilis, toxoplasmose, citomegalovírus, rubéola e herpes. Sabe-se que não existe terapia antiviral específica contra o VZIK, e a abordagem terapêutica de gestantes portadoras da infecção limita-se ao uso de antitérmicos e analgésicos. Orienta-se evitar anti-inflamatórios até que o diagnóstico de dengue seja descartado. Sobre a condução do pré-natal, não há necessidade de modificar o cronograma de consultas pré-natais para gestantes que foram infectadas pelo VZIK, mas é necessária a garantia de três exames ecográficos durante a gravidez para gestantes de baixo risco, e mensais para a gestante com infecção confirmada pelo VZIK. A via de parto é vaginal, e está liberado o aleitamento natural.
Subject(s)
Microcephaly/virology , Pregnancy Complications, Infectious , Zika Virus Infection , Female , Humans , Infant, Newborn , Microcephaly/diagnosis , Microcephaly/embryology , Microcephaly/therapy , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/therapy , Prenatal Care , Zika Virus Infection/diagnosis , Zika Virus Infection/therapy , Zika Virus Infection/transmissionABSTRACT
Purpose Our aim was to describe the changes observed by ultrasonography in uterine dimensions during the early puerperium among women who experienced an uncomplicated puerperium. Additionally, the influence of parity, mode of delivery, breastfeeding and birth weight on uterine involution was evaluated. Methods Ninety-one patients underwent an ultrasound examination on days 1 (D1), 2 (D2) and 7 (D7) of the postpartum period. The longitudinal, anteroposterior and transverse uterine diameters were measured, and the uterine volume was calculated by the formula: longitudinal diameter (LD) X anteroposterior diameter (APD) X transverse diameter (TD) X 0.45. The thickness and length of the uterine cavity were also measured. Results The uterine volume and the LD, APD and TD decreased by 44.8%, 20.9%, 11.8% and 20.0% respectively. The uterine cavity thickness was reduced by 23%, and the length of the cavity was reduced by 27.2% on D7. Uterine involution was correlated inversely with parity when the day of the postpartum period was not taken into account (p = 0.01). However, when the uterine involution was correlated to parity separately, with D1, D2 or D3, no correlations were found. A significant difference occurred at D2, when it was found that the uterus had a smaller volume following cesarean section compared with vaginal delivery (p = 0.04). The high birth weight and breastfeeding were significantly related to uterine involution (p ≤ 0.01 and p = 0.04). Conclusion The sonographic evaluation of the uterus in the early puerperium should consider birth weight, breastfeeding and parity, as well as the delivery route on D2, to identify abnormalities related to uterine involution.
Subject(s)
Postpartum Period/physiology , Ultrasonography , Uterus/diagnostic imaging , Uterus/physiology , Adolescent , Adult , Female , Humans , Organ Size , Uterus/anatomy & histology , Young AdultABSTRACT
Abstract Purpose Our aim was to describe the changes observed by ultrasonography in uterine dimensions during the early puerperium among women who experienced an uncomplicated puerperium. Additionally, the influence of parity, mode of delivery, breastfeeding and birth weight on uterine involution was evaluated. Methods Ninety-one patients underwent an ultrasound examination on days 1 (D1), 2 (D2) and 7 (D7) of the postpartum period. The longitudinal, anteroposterior and transverse uterine diameters were measured, and the uterine volume was calculated by the formula: longitudinal diameter (LD) X anteroposterior diameter (APD) X transverse diameter (TD) X 0.45. The thickness and length of the uterine cavity were also measured. Results The uterine volume and the LD, APD and TD decreased by 44.8%, 20.9%, 11.8% and 20.0% respectively. The uterine cavity thickness was reduced by 23%, and the length of the cavity was reduced by 27.2% on D7. Uterine involution was correlated inversely with parity when the day of the postpartum period was not taken into account (p= 0.01). However, when the uterine involution was correlated to parity separately, with D1, D2 or D3, no correlations were found. A significant difference occurred at D2, when it was found that the uterus had a smaller volume following cesarean section compared with vaginal delivery (p= 0.04). The high birth weight and breastfeeding were significantly related to uterine involution (p ≤ 0.01 and p= 0.04). Conclusion The sonographic evaluation of the uterus in the early puerperium should consider birth weight, breastfeeding and parity, as well as the delivery route on D2, to identify abnormalities related to uterine involution.
Resumo Objetivo Descrever as alterações observadas pela ultrassonografia nas dimensões uterinas durante o puerpério precoce em mulheres com evolução puerperal não complicada, considerando a influência da paridade, tipo de parto, amamentação e peso ao nascer sobre a involução uterina. Métodos Noventa e uma pacientes foram submetidas a exame ultrassonográfico nos dias 1 (D1), 2 (D2) e 7 (D7) do puerpério. Os diâmetros uterinos longitudinal, anteroposterior e transversal foram medidos, e o volume uterino foi calculado pela fórmula: diâmetro longitudinal (DL) X diâmetro anteroposterior (DAP) X diâmetro transverso (DT) X 0,45. A espessura e comprimento da cavidade uterina também foram medidos. Resultados O volume uterino e o DL, DAP e DT diminuíram 44,8%, 20,9%, 11.8% e 20,0% respectivamente no D7. A espessura da cavidade uterina reduziu em 23%, e o comprimento da cavidade foi reduzido em 27,2% no D7. A involução uterina se correlacionou inversamente com a paridade quando o dia do puerpério não foi levado em conta (p= 0,01). Uma diferença significativa foi encontrada em D2, quando se verificou que o útero tinha um volume menor no grupo submetido a cesariana em comparação com o parto vaginal (p= 0,04). O peso ao nascer elevado e amamentação apresentaram relação estatisticamente significativa com a involução uterina (p ≤ 0,01 e p= 0,04). Conclusão A avaliação ultrassonográfica do útero no puerpério precoce deve considerar o peso ao nascer, a amamentação e a paridade, assim como a via de parto no D2, para a identificação de anormalidades relacionadas à involução uterina.
Subject(s)
Humans , Female , Adolescent , Adult , Young Adult , Postpartum Period/physiology , Ultrasonography , Uterus/diagnostic imaging , Uterus/physiology , Organ Size , Uterus/anatomy & histologyABSTRACT
Magnetic resonance imaging (MRI) has been increasingly adopted in obstetrics practice in the past three decades. MRI aids prenatal ultrasound and improves diagnostic accuracy for selected maternal and fetal conditions. However, it should be considered only when high-quality ultrasound cannot provide certain information that affects the counseling, prenatal intervention, pregnancy course, and delivery plan. Major indications of fetal MRI include, but are not restricted to, morbidly adherent placenta, selected cases of fetal brain anomalies, thoracic lesions (especially in severe congenital diaphragmatic hernia), and soft tissue tumors at head and neck regions of the fetus. For fetal anatomy assessment, a 1.5-Tesla machine with a fast T2-weighted single-shot technique is recommended for image requisition of common fetal abnormalities. Individual judgment needs to be applied when considering usage of a 3-Tesla machine. Gadolinium MRI contrast is not recommended during pregnancy. MRI should be avoided in the first half of pregnancy due to small fetal structures and motion artifacts. Assessment of fetal cerebral cortex can be achieved with MRI in the third trimester. MRI is a viable research tool for noninvasive interrogation of the fetus and the placenta.
Subject(s)
Fetal Diseases/diagnostic imaging , Magnetic Resonance Imaging/methods , Prenatal Diagnosis/methods , Ultrasonography, Prenatal/methods , Central Nervous System/abnormalities , Central Nervous System/diagnostic imaging , Contraindications , Contrast Media , Female , Gadolinium , Hernias, Diaphragmatic, Congenital/diagnostic imaging , Humans , Neuroimaging/methods , Placenta Diseases/diagnostic imaging , Pregnancy , SafetyABSTRACT
Fetal surgery involves a large number of heterogeneous interventions that vary from simple and settled procedures to very sophisticated or still-in-development approaches. The overarching goal of fetal interventions is clear: to improve the health of children by intervening before birth to correct or treat prenatally diagnosed abnormalities. This article provides an overview of fetal interventions, ethical approaches in fetal surgery, and benefits obtained from antenatal surgeries.
Subject(s)
Fetus/surgery , Catheter Ablation/ethics , Catheter Ablation/methods , Female , Fetal Diseases/diagnostic imaging , Fetal Diseases/surgery , Fetoscopy/ethics , Fetoscopy/methods , Humans , Infant, Newborn , Internationality , Minimally Invasive Surgical Procedures/ethics , Minimally Invasive Surgical Procedures/methods , Obstetrics , Perinatal Care , Pregnancy , Societies, Medical , Ultrasonography, PrenatalABSTRACT
O desenho de um estudo pode ser definido como a forma em que se incluem e comparam os sujeitos da pesquisa com determinadas características. Os estudos são divididos habitualmente em experimentais e não experimentais (observacionais), onde a diferença está na possibilidade do investigador ter ou não controle sobre a exposição de um fator (agente etiológico ou terapêutico). Nos concentraremos aqui no estudo de caso-controle. Um estudo caso-controle é um estudo observacional para determinar se uma exposição está associada com um desfecho. De maneira simplificada, identificar um grupo conhecido por ter o desfecho (casos) e um grupo conhecido por não tê-lo (controles), olhando para trás no tempo para saber quais indivíduos em cada grupo tiveram a exposição e comparar a frequência da exposição no grupo caso com o grupo controle.(AU)
The study design can be defined as the way in which they include and compare the subjects participant with certain characteristics. The studies are usually classified as experimental and non-experimental (observational), whose difference is the possibility of the researcher to control the exposure of a factor (etiological or therapeutic agent). We will focus here on the case-control study. The cohort study is an observational study designed to help determine if an exposure is associated with an outcome. In short words, the case-control study identify a group known to have the outcome (cases) and a group known to be free of the outcome (controls). It looks back in time to learn which subjects in each group had the exposure and compare the frequency of the exposure in the case group to the control group.(AU)
Subject(s)
Humans , Case-Control Studies , Biomedical Research/methods , Observational Studies as Topic/methods , Pancreatic Neoplasms/epidemiology , Beer/adverse effects , Beer/statistics & numerical data , Alcohol Drinking/epidemiology , Bias , Odds RatioABSTRACT
OBJECTIVE: To identify significant predictors for adverse neonatal outcome in severe by compromised fetuses. METHODS: Consecutive premature fetuses at between 25 and 32 weeks' with severe placental insufficiency were examined prospectively. Inclusion criteria were: singletons; normal anatomy; abnormal umbilical artery Doppler pulsatility index; abnormal cerebroplacental ratio; middle cerebral artery pulsatility index (PI) Subject(s)
Fetal Weight
, Middle Cerebral Artery/diagnostic imaging
, Placental Insufficiency/diagnostic imaging
, Ultrasonography, Prenatal/methods
, Umbilical Arteries/diagnostic imaging
, Female
, Humans
, Infant, Newborn
, Logistic Models
, Pregnancy
, ROC Curve
, Ultrasonography, Doppler, Color